Re: Re: Distinguishing between true and "official" HIV infection 12 July 2003
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Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David, Causer, Helman Alfonso

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Re: Re: Re: Distinguishing between true and "official" HIV infection

It is the role of the doctor, not the patient, to interpret tests

Brian Foley quotes the Perth Group: "Do patients really play a role in interpreting their own tests?"

 He responds “And my answer is that of course they do in most cases, and they always should.  The patient always knows more about the patient's history than the doctor does.  An accurate diagnosis depends on more than test results, it also requires putting those results into the context of the whole picture…likewise for HIV antibody testing, the person being tested knows more about their history of sexual activities, IV drug use and needle sharing, and transfusions”. 

There is no doubt the patient does know more about his medical history than his doctor.  The doctor’s skill lies in obtaining that history and formulating it in such a manner he can decide whether or not a test is likely to assist arriving at a diagnosis.  On many occasions no test is warranted.  The greatest physician who ever lived, Sir William Osler, taught his students,  “Talk to the patient long enough and he will tell you what is wrong with him”.  However, once a test is performed the patient plays no role in interpretation.  Not even if the patient is a doctor.  A visit to the coronary care unit of any hospital will not reveal patients sitting up in bed studying their chest X-rays or ECGs.

 Brian Foley appears to believe particular antibody test results (using criteria of his choosing), indicates HIV infection if the person being tested has a history of “sexual activities, IV drug use and needle sharing, and transfusions”.  What Brian avoids is telling us how he interprets the same test result in a person who is not in a risk group and is healthy.

 If a positive test in a healthy, no risk person does not indicate HIV infection then how does Brian reconcile this with the advice from the CDC that “HIV testing consists of an initial screening with two types of tests commonly used to detect HIV infection. The most commonly used initial test is an enzyme immune assay (EIA) or the enzyme-linked immunosorbent assay (ELISA).  If EIA test results show a reaction, the test is repeated on the same blood sample. If the sample is repeatedly the same result or either duplicate test is reactive, the results are "confirmed" using a second test such as the Western blot.  This more specific (and more expensive) test can tell the difference between HIV antibodies and other antibodies that can react to the EIA and cause false positive results.  False positive EIA results are uncommon, but can occur.  A person is considered infected following a repeatedly reactive result from the EIA, confirmed by the Western blot test” (emphasis added).  http://www.hivtest.org/subindex.cfm?FuseAction=FAQ#2

The CDC assertion makes no mention of the patient’s history, healthy or otherwise.  For the CDC, as for all HIV experts, the tests are considered virtually 100% specific rendering clinical data irrelevant.

At www.cdc.gov/mmwr/preview/mmwrhtml/mm4923a2.htm we read: In 1999 “Of the estimated 800,000--900,000 persons infected in the United States, approximately one third have yet to be diagnosed”. At www.cdc.gov/mmwr/preview/mmwrhtml/mm5225a1.htm the CDC report: “In  2000, an estimated 850,000--950,000 persons in the United States were living with HIV, and approximately one fourth of these persons did not know they were infected (1)”.

In reference 1 (www.cdc.gov/mmwr/preview/mmwrhtml/mm4923a2.htm), “During January 1997--September 1998, 615 persons with HIV infection diagnosed and reported met the criteria for the study; these persons represented 15% of all persons with HIV infection diagnosed and reported during this period from Alabama, New Jersey, and Tennessee.  Of the 543 persons determined eligible after follow-up by state health departments, 180 (33%) completed interviews, 127 (23%) refused to be interviewed, and 235 (43%) could not be located.  Among persons with known dates, 148 (86%) of 173 were interviewed within 12 months of the self-reported date they learned they were HIV-infected (median: 6 months)”.

Twenty-three (28%) of 81 males and 69 (70%) of 99 females could not be classified as having recognised transmission risk or as having sexual contact with an HIV-infected partner or one with a documented transmission risk…Among 68 males stating a primary reason for being tested, the leading reasons were because a doctor or friend told them to be tested (28%) and because they were worried they might be infected even though they were not sick (22%).  Among 90 females stating a primary reason for testing, the leading reasons were because of pregnancy care (33%) and because a doctor or friend told them to be tested (18%)…Of 180 persons interviewed, 151 (84%) reported receiving medical care for HIV infection since diagnosis.  Among the 27 persons who responded that they had not received medical care for their HIV infection since diagnosis, 13 (48%) reported feeling well and not thinking it was important to seek medical care right away, and 12 (44%) reported not wanting to think about being HIV-positive as reasons for postponing seeking health care right away.

 Clearly, in this study there are a number of seropositive, healthy people devoid of risk factors.  (We could also argue “could not be classified…” is CDCspeak for “has not admitted risk factors to the study authors”).  This raises a number of questions: 

  1. How should a physician interpret his healthy, no risk patient’s positive antibody test?  Or, if we follow Brian’s method, how should the patient interpret his own test?
  2. Although the criteria for a positive “confirmatory” Western blot are not stated they are likely to be those of the CDC, that is, two reactive bands chosen from p24, gp41 and gp120/160.  These would not “confirm” HIV infection in Australia and, depending on the exact band pattern, in other countries.  How should such tests be interpreted if a patient were to emigrate, for example, to Australia, where combinations of four bands are required?
  3. Does Brian Foley agree with the CDC that “A person is considered infected following a repeatedly reactive result from the EIA, confirmed by the Western blot test” regardless of the patient’s history?
  4. For test manufacturers such as Abbott Laboratories [1], “Specificity [is] based on an assumed zero prevalence of antibody to HIV-1 and/or HIV-2 in random donors”.  If this is the case must not we also conclude that positive tests in all healthy persons, including those in the above CDC study, are false positives?  It is possible to imagine that some of the healthy, no risk persons in this study could have been “random donors”.   If they are regarded as false positives by one group of evaluators how can they be regarded infected by another?  How would physicians, patients and their relatives react to this conundrum?  Would Brian Foley recommend antiretrovirals to such individuals?  Or their unborn children?
  5. In regard to point 4, since the  vast majority of seropositive individuals are clinically healthy, how can we avoid concluding “the global burden of HIV” is a gross misapprehension?
  6. If the American Red Cross, the CDC, the Association of State and Territorial Public Health Laboratory Directors, the FDA, The Consortium for Retrovirus Serology Standardization, the HIV experts and biotechnology companies cannot agree on a definition of a positive “confirmatory” Western blot, what hope do physicians or their patients have for interpreting these tests?

Brian also doubts that in the MultiCenter AIDS Cohort Studies a single “strong”  Western blot band was considered “proof” of HIV infection.  He also states “A single band may have been all that was required for enrollment in the study, but scientists rarely speak of “proof” of anything”.

  1. The 4954 men enrolled in the MACS were enrolled beginning in early 1984, that is, before the antibody tests were developed and long before they were introduced into routine, clinical practice.
  2. In “determining antibody to HIV…All specimens for which ELISA results suggested seroconversion, (ie increase from <0.5 to ³ 0.5 were examined by immunoblot techniques.  A score of 0 was assigned for a negative band, 1 for a weakly reactive band, 2 for a moderately reactive band, and 3 for a strongly reactive band to p15, p24, p31, p45, p53, p55, p64 or p120.  The scores of all bands were summed and a value ³ 3 was defined as positive, 2 as equivocal and £ 1 as negative.  [Even this has changed.  Nowadays one band is considered indeterminate].  The validity of this method has been evaluated by prospective assessment in this cohort”.  Thus (i) one “strong” band was considered a positive Western blot;  (ii) these data again show that the gold standard for the antibody tests was clinical data and not HIV itself [2].
  3. Since the band criteria for a positive WB have changed over time, including in the MACS, it is possible there are a number of gay men, alive or dead, who nowadays would not be considered HIV infected based on their earlier tests.   If they are sick or dead, why?
  4. Scientists may or may not “rarely speak of proof” but do the CDC criteria of a twice reactive ELISA/single positive WB prove HIV infection or not?

Lastly, Brian would like to know how many men in the MACS had one “strong” band.  So would the Perth Group, especially given (3).  Unfortunately, the individual Western blot patterns are not published.  Brian’s “understanding” is that “almost all HIV-infected people produce strong immunological responses to many HIV proteins during the course of their infection, and almost none (perhaps less than 2%?) produce an immunoglobulin response to only one of the HIV-1 proteins”.  Brian may be right but upon what data is his “understanding” based?  The fact is that once a laboratory or institution or country sets its criteria for a positive Western blot then any patterns not fulfilling these criteria are either negative or indeterminate.  According to HIV expert Anthony Fauci, “There are two possible explanations for an indeterminate western blot result.  The most likely explanation is that the patient has antibodies that cross react with one of the proteins of HIV…the least likely explanation…is that the individual is infected with HIV” (Harrison’s Principles of Internal Medicine, 13th edition, page 1584).  It is also an inescapable fact that the positive criteria under one laboratory, institution or country may be indeterminate under another.  In this regard, Brian’s explanations about changing band patterns during the early days of an individuals' infection or percentages of seropositives who do not have “strong immunological responses” are irrelevant.  If Brian believes that sooner or later all WB band patterns “evolve” into a particular pattern he asserts diagnostic of HIV infection, (a) what pattern is it?  (b) what is his proof; (c) why isn’t this pattern universal?

Would anyone entertain the ECG criteria for an acute myocardial infarction differing between countries?  Or the radiological criteria for an acute, traumatic dissection of the thoracic aorta?  Could the same patient have an AMI or aortic rupture in one country but not in another?  Can Brian Foley, or anyone else, please explain how the diagnosis of infection with the same virus using the same antibody test can be based on ten or more different sets of criteria?

  1. Packet Insert Axsym system (HIV-1/HIV-2).  Abbott Laboratories Diagnostics Division.  100 Abbott Park Rd. Abbott Park.  Illinois: United States of America.  1988, 1998. http://aids-kritik.de/aids/diverses/abbott-hiv-test.htm
  2. Kingsley LA, Kaslow R, Rinaldo CR, Detre K, Odaka N, VanRaden M, et al. Risk factors for seroconversion to human immunodeficiency virus among male homosexuals. Lancet 1987;i:345-348

Competing interests:   None declared